Large-Scale Reconstruction of Microvascular Networks and the Surrounding Cellular

描述(由申请人提供)：为计算机科学家David Mayerich博士提出职业发展计划，他致力于在生物医学工程领域发展跨学科的职业生涯，重点是亚微米分辨率的大规模数据集的收集和分析。他的研究生研究领域是计算机可视化和光学成像，在这些领域，他的工作导致了刀口扫描显微镜(KESM)原型的开发。这是第一台能够以亚微米分辨率成像三维宏观组织体积的仪器，同时提供接近大多数现代计算机系统传输速度的数据速率。 自获得博士学位以来，迈耶里奇博士在伊利诺伊大学厄巴纳-香槟分校贝克曼高级科学与技术研究所担任博士后研究员，与生物学家和生物医学工程师合作，开发用于大数据集分割和分类的工具。这为解决跨学科社区可用的计算工具的需求和限制提供了经验。 这项提案的指导阶段的目标是为迈耶里奇博士提供机会，让他成为Farsight工具包的开发人员。Farsight工具包是一个开源分割工具包，专注于开发专门为处理显微镜数据集中发现的独特结构而量身定做的计算机视觉算法。这一项目是由李嘉诚教授指导的。 Badrinath Roysam在休斯顿大学学习，并在NIH赞助的神经元分割王冠挑战赛中获得第一名。Mayerich博士将利用他之前在生物医学分段、基于GPU的计算和高效数据结构方面的经验，帮助使Farsight工具包可扩展到使用下一代高通量成像技术产生的TB级数据集。Mayerich博士将接受Farsight工具包中使用的算法和技术方面的指导，以及在协作软件开发项目中工作的宝贵经验。 独立阶段的目标是使用最近发展的成像技术，以及可扩展的分割算法，来构建完整的小鼠器官微血管模型。KESM的最新进展表明，在不到50小时的时间内可以采集到1厘米3组织样本的亚微米图像。这些图像具有(A)完整重建整个器官的微血管网络以及(B)细胞胞体相对于该网络的几何分布所必需的分辨率和质量。描述蜂窝和 微血管关系在包括神经退行性疾病和肿瘤生长在内的几种疾病中都有影响，以及在组织工程和血管生成药物和治疗的定量分析中的临床应用。

DESCRIPTION (provided by applicant): A career development plan is proposed for Dr. David Mayerich, a computer scientist who is committed to developing an interdisciplinary career in biomedical engineering, with a focus on the collection and analysis of large-scale data sets at sub-micrometer resolution. His graduate research was in the areas of computer visualization and optical imaging, where his work lead to the development of the prototype Knife-Edge Scanning Microscope (KESM). This is the first instrument capable of imaging three-dimensional macro-scale tissue volumes at sub-micrometer resolution while providing a data rate approaching the transfer speed of most modern computer systems. Since receiving his Ph.D., Dr. Mayerich worked as a postdoctoral fellow at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign, where he has worked with biologists and biomedical engineers to develop tools for the segmentation and classification of large data sets. This provided experience in addressing the needs and limitations of the computational tools available to the interdisciplinary community. The goal of the mentored phase of this proposal is to provide Dr. Mayerich with the opportunity to work as a developer for the FARSIGHT Toolkit. The FARSIGHT Toolkit is an open-source segmentation toolkit that focuses on developing computer vision algorithms specifically tailored to deal with the unique structures found in microscopy data sets. This project is directed by Prof. Badrinath Roysam at the University of Houston, and was awarded first-place in the NIH-sponsored DIADEM Challenge in neuron segmentation. Dr. Mayerich will use his previous experience in biomedical segmentation, GPU-based computing, and efficient data structures to help make the FARSIGHT Toolkit scalable to the terabyte-scale data sets produced using next-generation high-throughput imaging techniques. Dr. Mayerich will receive mentoring in the algorithms and techniques used in the FARSIGHT Toolkit, as well as valuable experience working on a collaborative software development project. The goal of the independent phase is to use recently developed imaging techniques, along with scalable segmentation algorithms, to construct complete microvascular models of mouse organs. Recent advances in KESM demonstrate that sub-micrometer images of 1cm3 tissue samples can be collected in less than 50 hours. These images have the resolution and quality necessary for (a) complete reconstruction of microvascular networks in whole organs, and (b) the geometric distribution of cell soma in relation to this network. Models describing cellular and microvascular relationships have implications in several diseases, including neurodegenerative disease and tumor growth, as well as clinical applications in tissue engineering and the quantitative analysis of angiogenic drugs and therapies.